(1) Field of the Invention
The present invention relates to the use of two tandem microfiltration (MF) steps in a process for making recombinant insulin.
(2) Description of Related Art
Tangential flow filtration (TFF) is a robust and versatile separation technique used in biopharmaceutical manufacturing. TFF is typically categorized as microfiltration (MF; pore sizing in microns) or ultrafiltration (UF; pore sizing in nominal molecular weight limit). MF processes have been classically employed in harvest and primary recovery, whereas UF processes have been largely used as polishing steps for buffer exchange or concentration (Marichal-Gallardo and Alvarez; van Reis and Zydney 2001).
Successful scale-up is a key challenge in implementation of microfiltration processes. Most commonly, MF unit operations are scaled on constant load factor (volume or mass per filter area), membrane channel geometry, path length, crossflow velocity, and transmembrane pressure (TMP) (Marichal-Gallardo and Alvarez 2012). However, performance upon scale-up is difficult to predict, heavily dependent on the nature of the feedstock, and often must be optimized empirically (Roush and Lu 2008; Saxena et al. 2009). The most common operational challenge for MF processes is filter fouling due to deposition of insoluble material on the membrane surface or inside membrane pores, which increases flow resistance (Marichal-Gallardo and Alvarez 2012; van Reis and Zydney 2007). Fouling is typically quantified as decreased flux at constant TMP or increased TMP at constant flux. Although models such as pore blockage, pore constriction, and cake filtration have been developed to aid in mitigation of fouling (Ho and Zydney 2000; Palacio et al. 2002), efficient scale-up remains a significant challenge.